The overall goal of the project is to identify and characterize macrophage products of potential importance in immune and inflammatory responses in order to manipulate these responses for clinical benefit. Differential screening of a cDNA library prepared from a mouse macrophage- like cell line led to the identification of 11 mRNA species of increased abundance following exposure to gamma-interferon. Two of these mRNA species, designated Mig and crg-2 encode previously undescribed members of a newly-defined family of small secreted proteins, termed chemokines, that includes platelet factor 4, melanoma growth stimulatory activity (MGSA/gro) and IL-8 among others. Using the mouse MuMig cDNA probe, a new human member of the family has been discovered. Work to date has demonstrated that the MuMig and HuMig mRNAs accumulate in monocytic cells specifically in response to gamma interferon, while Crg- 2/IP-10 can respond to alpha interferon and to lipopolysaccharide as well. Following intraperitoneal injection of gamma interferon into mice, MuMig is induced in a range of tissues including most prominently liver, spleen, thymus, and uterus. Chinese hamster ovary cell lines were derived that overexpress the MuMig, HuMig, Crg-2 and IP-10 proteins. Using a Western blot assay, the MuMig and HuMig proteins have been purified. By PAGE, the Mig proteins show multiple species with mobilities corresponding to 16-20 kDa for MuMig and 9.5-35 kDa for HuMig. The size heterogeneity of the HuMig protein is due to proteolytic processing of the carboxy terminus. Functional studies have revealed that activated T cells, but not neutrophils or monocytes, are targets for HuMig. Ongoing work is concentrating on determining the range of biological effects of Mig on T cells; on additional biochemical characterization of Mig and identification of Mig receptors; on the role of Mig in the response to infection; on a possible role for chemokines in embryogenesis; and on identifying additional novel chemokines.